SPID#: 41 The relative antithrombotic and antihemostatic effects of an orally active synthetic inhibitor of FXa, (2S)-2-[4-[[(3S)-1-acetimidoyl-3- pyrrolidinyl]oxy]phenyl]-3-(7-amidino-2-naphthyl) propionic acid hydrochloride pentahydrate (APAP), has been evaluated in baboons using a two-component thrombogenic device inducing the concurrent formation of both arterial-type platelet-rich (on segments of vascular graft) and venous-type fibrin-rich thrombus (in expanded chambers exhibiting disturbed flow) when interposed in chronic exteriorized arteriovenous (AV) femoral shunts flowing at 40 mL/min. Thrombus formation was compared for oral vs parenteral APAP by measuring 111In-platelet deposition, 125I-fibrin accumulation, thrombotic obstruction of flow, and circulating levels of blood biochemical markers of thrombosis. Both oral and infused APAP reduced platelet deposition in a dose-dependent manner for venous-type fibrin-rich thrombus. However, neither platelet deposition nor fibrin accumulation were reduced significantly for platelet-rich arterial-type thrombus formation on segments of vascular graft (p>0.1 in all cases). Oral and infused APAP prolonged the APTT, and prevented thrombus-dependent elevations in plasma fibrinopeptide A (FPA), thrombin-antithrombin III complex (TAT), beta-thromboglobulin (_TG), and platelet factor 4 (PF4) levels. Additionally, APAP produced dose-dependent inhibition of activated factor X bound to thrombus on segments of vascular graft interposed in exteriorized AV shunts for 15 min. Bleeding time measurements were not prolonged by APAP at any of the doses administered (p>0.5). We conclude that oral APAP inhibits the formation of venous-type fibrin-rich thrombus by inactivating bound and soluble FXa without impairing platelet hemostasis. In related studies, we have demonstrated that intravenous injections of inactivated factor VIIa, a competitive inhibitor of tissue-factor-dependent activation of coagulation factor X, reduced vascular lesion and vascular thrombosis during carotid endarterectomy or femoral artery balloon catheter angioplasty.